Differential release of serotonin without comparable histamine under diverse conditions in the rat mast cell.

Pretreatment of mast cells with various psychotropic agents was shown to permit preferential release of serotonin without substantial release of histamine or massive degranulation. Differential release involved both endogenous, granule-stored serotonin, and exogenous radiolabeled serotonin that had been taken up by the cell. This phenomenon occurred in mast cells stimulated to secrete with suboptimal concentrations of the classic mast cell secretagogue compound 48/80, was associated with drugs of several different structures and known mechanisms of action, and could be inhibited by certain prostaglandins. Furthermore, differential release of serotonin occurred in mast cells of retired breeders without the use of drugs or other exogenous agents. Light microscopic studies of mast cells undergoing differential release showed minimal degranulation, indicating that most of the serotonin release did not occur via classic exocytosis. The ability of mast cell to selectively release serotonin, by a mechanism unlike that occurring in allergic anaphylactic secretion, constitutes one of the first instances of differential release from secretory cells, suggests a new mechanism of release of secretory products, and expands the potential role of mast cells in the pathophysiology of the body.